Increased Wnt5a/ROR2 signaling is associated with chondrogenesis in meniscal degeneration.

The aim of the present study was to investigate the association between chondrogenic differentiation and Wnt signal expression in the degenerative process of the human meniscus. Menisci were obtained from patients with and without knee osteoarthritis (OA), and degeneration was histologically assessed using a grading system. Immunohistochemistry, real-time polymerase chain reaction (PCR), and Western blot analysis were performed to examine the expressions of chondrogenic markers and of the components of Wnt signaling. Histological analyses showed that meniscal degeneration involved a transition from a fibroblastic to a chondrogenic phenotype with the upregulation of SOX9, collagen type II, collagen type XI, and aggrecan, which were associated with increased Wnt5a and ROR2 and decreased TCF7 expressions. OA menisci showed significantly higher expressions of Wnt5a and ROR2 and significantly lower expressions of AXIN2 and TCF7 than non-OA menisci on real-time PCR and Western blot analysis. These results potentially demonstrated that increased expression of Wnt5a/ROR2 signaling promoted chondrogenesis with decreased expression in downstream Wnt/ß-catenin signaling. This study provides insights into the role of Wnt signaling in the process of meniscal degeneration, shifting to a chondrogenic phenotype. The findings suggested that the increased expression of Wnt5a/ROR2 and decreased expression of the downstream target of Wnt/ß-catenin signaling are associated with chondrogenesis in meniscal degeneration.

Requirement of the 3'-UTR-dependent suppression of DAZL in oocytes for pre-implantation mouse development.

Functional oocytes are produced through complex molecular and cellular processes. In particular, the contribution of post-transcriptional gene regulation mediated by RNA-binding proteins (RBPs) is crucial for controlling proper gene expression during this process. DAZL (deleted in azoospermia-like) is one of the RBPs required for the sexual differentiation of primordial germ cells and for the progression of meiosis in ovulated oocytes. However, the involvement of DAZL in the development of follicular oocytes is still unknown. Here, we show that Dazl is translationally suppressed in a 3'-UTR-dependent manner in follicular oocytes, and this suppression is required for normal pre-implantation development. We found that suppression of DAZL occurred in postnatal oocytes concomitant with the formation of primordial follicles, whereas Dazl mRNA was continuously expressed throughout oocyte development, raising the possibility that DAZL is dispensable for the survival and growth of follicular oocytes. Indeed, follicular oocyte-specific knockout of Dazl resulted in the production of normal number of pups. On the other hand, genetically modified female mice that overexpress DAZL produced fewer numbers of pups than the control due to defective pre-implantation development. Our data suggest that post-transcriptional suppression of DAZL in oocytes is an important mechanism controlling gene expression in the development of functional oocytes.

Bone mineral density distribution in the proximal femur and its relationship to morphologic factors in progressed unilateral hip osteoarthritis.

Although an adverse relationship between osteoporosis and osteoarthritis (OA) has been reported, it remains controversial. In most previous reports of OA, bone mineral density (BMD) changes in the subtrochanteric region have not been clarified, whilst BMD of the femoral neck and trochanteric region has been well investigated. In our current study, we investigated the BMD ratio compared to the contralateral side in the whole proximal femurs of hip OA patients. We aimed to clarify the morphologic factor that may influence these BMD ratios. We performed dual energy X-ray absorptiometry (DEXA) analysis of 69 hip joints from unilateral progressed OA cases. The minimum joint space, center edge angle, Sharp angle, acetabular head index, neck-shaft angle, and leg length discrepancy were also measured as radiographic factors. The correlation between BMD ratio and radiographic morphologic factors was then evaluated by logistic regression. The BMD ratio was higher in the femoral neck than in the distal region. In terms of radiographic factors, the neck-shaft angle was revealed to influence the decreased BMD ratio in the distal subtrochanteric part, whilst the leg length discrepancy and Sharp angle showed a relationship with the increased BMD ratio in the proximal neck region. The discrepancy in the BMD ratio between the femoral neck and the distal subtrochanteric region in the proximal femur is influenced by several morphologic factors.